The preparation of glucagon analogues and derivatives suitable for structure-function studies of this peptide hormone will be made using a variety of semi-synthetic methods. Glucagon analogues which are modified at the C-terminal and amino terminal regions and at selected functional groups will be prepared. The compounds will be examined for their biological activities and for their ability to bind to liver plasma membrane hormone receptors. We are particularly interested in obtaining a glucagon analogue which will act as an antagonist (competitive inhibitor) to the hormone for potential use in treatment of hyperglycemia in diabetes and for studying the mechanism of glucagon hormone action in normal and diabetic states. Other desirable compounds would include analogues which are more active than the hormone itself, partial agonists, radiolabeled derivatives suitable for binding studies to receptors for the hormones and for degredation studies, and analogues which are longer lasting than the native hormone. Studies of the dynamic and structural properties of interesting analogues will be made and the results compared with those of glucagon.